Autism Spectrum Disorder (ASD) is one of the most serious psychiatric disorders of childhood. ASD involves deficits in social functioning, communication, and restricted interests/repetitive behaviors. In the United States, it is estimated that ~1/100 children are affected with ASDs. The individual and societal costs are enormous, and there is no known cure. Investigating the neuroscience of ASDs in childhood and infancy is vital because very early behavioral and educational interventions, starting at 18-24 months of age, have been shown to improve outcome. With still earlier diagnosis, interventions might begin even sooner, with potentially further dramatic improvements in outcomes. The fellow’s long-range objective is to use measures of functional connectivity to understand more about the neural basis of autism and to try to build a pre-symptomatic diagnostic classifier. Recent functional connectivity magnetic resonance imaging (fcMRI) studies have found alterations in brain functional connections that may be the result of these early brain growth abnormalities. However, the MRI environment can prove intolerable for young ASD children due to noise, claustrophobia, and the need to lie supine and still. Diffuse optical tomography (DOT) can record evoked brain function in enriched or clinical environments. Functional connectivity DOT (fcDOT) for unconstrained neuroimaging in naturalistic settings would meet a central need in ASD. The main goal is to develop fcDOT methods to map brain networks of subjects with ASD and to determine the early mechanisms of brain dysfunction that lead to known indicators of ASD. The research aims: (1) to establish functional connectivity analysis methods of fcDOT in normal adults, and (2) to establish the feasibility of applying fcDOT to ASD children. We will validate network analyses for fcDOT against identical analyses of functional connectivity magnetic resonance imaging (fcMRI) data that are acquired from the same subjects. The team will then perform a feasibility study on ASD children. Success with this proposal will provide proof of principle for fcDOT and provide the basis for a future larger-scale studies adapting fcDOT for use in infants who are at risk for autism and in older ASD subjects with MRI scanner contraindications. This translational work will aim both to improve the fundamental understanding of the ASD pathophysiology and to develop a tool for potential use in early diagnosis and therapeutic monitoring of ASD subjects